The development of methodologies for enhancing dissolution and absorption of active ingredients is a major field of pharmaceutical formulation research. As generally defined, dissolution is the rate and extent to which an active ingredient enters into solution. Absorption is generally defined as the rate and extent to which the active ingredient moves from its site of administration to the site of action or general circulation. Absorption usually involves a passive diffusion of the active ingredient across a mucosal membrane.
Although in a few rare instances, very fine, non-dissolved particles may be absorbed into the body of a mammalian subject by special processes, most often active ingredients must dissolve before absorption can take place. However, in formulating pharmaceutical compositions, the goals of rapid absorption and dissolution of active ingredients are often difficult to reconcile. Thus, the environment that favors dissolution may sometimes inhibit absorption and vice versa.
Good examples of this often-competing relationship may be found in studying the influence of pH, which is the measure of concentration of the H+ ions, on dissolution and/or absorption of active ingredients. Many formulation techniques focus on the pH of the pharmaceutical compositions and dosage forms, and/or the pH environment at various sites in the body. However, even though pH is often important, standard pharmaceutical practice views the pH requirements for dissolution and absorption as somewhat contradictory. For example, Physical Pharmacy by Alfred Martin, Lea and Febiger, 4th Ed. (1993) teaches that a lower pH enhances the dissolution of weakly basic drugs while a higher pH enhances their absorption. Thus, the standard pharmaceutical practice often involves selecting a pharmaceutical dosage form with a pH that is a compromise between the pH that favors dissolution and the pH that favors absorption. Alternatively, the pH is selected to favor either the dissolution or the absorption, whichever is considered to be the rate-determining step in delivering the drug to its site of action.
The drugs that benefit from such pH adjustments are usually weakly basic or weakly acidic compounds. They make up a large proportion of available drugs and fall into numerous therapeutic classes. Usually, the drugs are delivered in either liquid or solid form. With respect to liquid pharmaceutical preparations, the pH of the liquid may be directly adjusted prior to administration to achieve the desired degree of dissolution of the active ingredient. With respect to the solid drug delivery vehicles such as the dosage forms, the dissolution typically takes place in vivo, and the modification of the pH is usually achieved by selecting the content of the dosage form. For example, an appropriate salt form of the drug may be used to improve the dissolution. In both modes of administration, however, the selected pH is rarely optimal for both dissolution and absorption of the active ingredient.
Therefore, there is a need for a method of administration that facilitates both absorption and dissolution of active ingredients.